Oxidized coenzyme Q10, which is a benzoquinone derivative widely distributed in the biological world, is also called vitamin Q because of its vitamin-like function and is an ingredient acting as a nutrient in restoring the cell activity that has been weakened to its healthy condition and rejuvenating the body. On the other hand, reduced coenzyme Q10, which is derived from oxidized coenzyme Q10 by two-electron reduction, is as white crystals as compared with oxidized coenzyme Q10 being as orange-colored crystals. Reduced coenzyme Q10 and oxidized coenzyme Q10 are known to be localized in the mitochondrion, lysosome, Golgi body, microsome, peroxisome, and cell membrane, among others, and involved, as constituents of the electron transport system, in ATP production and activation, in vivo antioxidant activity, and membrane stabilization; they are thus substances indispensable for body function maintenance.
It is known that reduced coenzyme Q10 can be prepared by producing coenzyme Q10 in the conventional manner, for example by synthesis, fermentation, or extraction from natural products, and concentrating a reduced coenzyme Q10-containing eluate fraction resulting from chromatography (JP-Hei-10-109933-A). On that occasion, as described in the above-cited publication, the chromatographic concentration may be carried out after reduction of oxidized coenzyme Q10 contained in the reduced coenzyme Q10 with a reducing agent such as sodium borohydride or sodium dithionite (sodium hyposulfite), or reduced coenzyme Q10 may be prepared by reacting the reducing agent mentioned above with an existing highly pure grade of coenzyme Q10 (oxidized form).
However, the thus-obtained reduced coenzyme Q10 cannot always be favorably crystallized without trouble but tends to occur as a low-purity crystalline, semisolid, or oily product containing such impurities as oxidized coenzyme Q10. Moreover, even when crystallization could be achieved somehow, some troubles are occurred due to its poor slurry properties, etc. For example, poor slurry fluidity causes stirring trouble or difficulty in brushing away from a crystallization container, and poor filterability requires long period of time for crystal separation. Furthermore, solubility of reduced coenzyme Q10 in various organic solvents tends to be high and there is such a problem that the crystallization yield is not always high.
In addition, reduced coenzyme Q10 has a characteristic of being readily oxidized into oxidized coenzyme Q10 by molecular oxygen. On a commercial production scale, complete oxygen elimination is very difficult to achieve and, furthermore, fairly long periods of time are required for individual operations, unlike laboratory scale production, so that residual oxygen exerts a great adverse effect. Prolonged time of an isolation process increases the risk of the above-mentioned oxidation, and is directly connected with such yield and quality problems as the formation of hardly eliminable oxidized coenzyme Q10 and immixture of the oxidized coenzyme Q10 into the product.
Under such circumstances, it has been strongly desired to establish a crystallization method for improving slurry properties and crystalline properties thereby producing reduced coenzyme Q10 with sufficient filterability in a high yield, and to establish a production method in which an isolation process including a crystal separation or the whole process including said isolation process, for producing highly pure reduced coenzyme Q10, are shortened and simplified.